NM_005219.5(DIAPH1):c.2030C>T (p.Pro677Leu) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 9, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001968507.4

Allele description [Variation Report for NM_005219.5(DIAPH1):c.2030C>T (p.Pro677Leu)]

NM_005219.5(DIAPH1):c.2030C>T (p.Pro677Leu)

Gene:

DIAPH1:diaphanous related formin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q31.3

Genomic location:

Preferred name:

NM_005219.5(DIAPH1):c.2030C>T (p.Pro677Leu)

HGVS:

NC_000005.10:g.141573820G>A
NG_011594.2:g.50236C>T
NM_001079812.3:c.2003C>T
NM_001314007.2:c.2030C>T
NM_005219.5:c.2030C>TMANE SELECT
NP_001073280.1:p.Pro668Leu
NP_001300936.1:p.Pro677Leu
NP_005210.3:p.Pro677Leu
LRG_1117t1:c.2003C>T
LRG_1117t2:c.2030C>T
LRG_1117:g.50236C>T
LRG_1117p1:p.Pro668Leu
LRG_1117p2:p.Pro677Leu
NC_000005.9:g.140953387G>A

Protein change:

P668L

Links:

dbSNP: rs761912885

NCBI 1000 Genomes Browser:

rs761912885

Molecular consequence:

NM_001079812.3:c.2003C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001314007.2:c.2030C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_005219.5:c.2030C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Autosomal dominant nonsyndromic hearing loss 1
Synonyms:: KONIGSMARK SYNDROME; Deafness, autosomal dominant 1; DEAFNESS, AUTOSOMAL DOMINANT 1, WITH OR WITHOUT THROMBOCYTOPENIA
Identifiers:: MONDO: MONDO:0007424; MedGen: C1852282; Orphanet: 90635; OMIM: 124900

Name:: Progressive microcephaly-seizures-cortical blindness-developmental delay syndrome
Synonyms:: Seizures, cortical blindness, and microcephaly syndrome
Identifiers:: MONDO: MONDO:0014714; MedGen: C5567650; OMIM: 616632

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002246272	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 9, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002246272

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 9, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002246272.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Not Available"; Align-GVGD: "Not Available". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 1462500). This variant has not been reported in the literature in individuals affected with DIAPH1-related conditions. This variant is present in population databases (no rsID available, gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 677 of the DIAPH1 protein (p.Pro677Leu).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

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