NM_003673.4(TCAP):c.223G>A (p.Gly75Ser) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Mar 12, 2019
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000183929.5

Allele description [Variation Report for NM_003673.4(TCAP):c.223G>A (p.Gly75Ser)]

NM_003673.4(TCAP):c.223G>A (p.Gly75Ser)

Gene:

TCAP:titin-cap [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q12

Genomic location:

Preferred name:

NM_003673.4(TCAP):c.223G>A (p.Gly75Ser)

Other names:

p.G75S:GGC>AGC

HGVS:

NC_000017.11:g.39665828G>A
NG_008892.1:g.5483G>A
NG_042278.1:g.2848G>A
NM_003673.4:c.223G>AMANE SELECT
NP_003664.1:p.Gly75Ser
NP_003664.1:p.Gly75Ser
LRG_210t1:c.223G>A
LRG_210:g.5483G>A
LRG_210p1:p.Gly75Ser
NC_000017.10:g.37822081G>A
NM_003673.3:c.223G>A

Protein change:

G75S

Links:

dbSNP: rs753744791

NCBI 1000 Genomes Browser:

rs753744791

Molecular consequence:

NM_003673.4:c.223G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000236417	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Feb 19, 2018)	germline	clinical testing	Citation Link,
SCV003827083	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 12, 2019)	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

SCV000236417

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Feb 19, 2018)

germline

clinical testing

Citation Link,

SCV003827083

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 12, 2019)

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From GeneDx, SCV000236417.9

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

Description

The G75S variant has not been published as pathogenic or been reported as benign to our knowledge. G75S has been identified in one other individual referred for cardiomyopathy genetic testing at GeneDx; however, that individual also harbored a pathogenic variant in a different gene. The G75S variant is observed in 4/22984 (0.02%) alleles from individuals of African background in large population cohorts (Lek et al., 2016). Nevertheless, the G75S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, in-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect.

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

From Revvity Omics, Revvity, SCV003827083.2

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

#	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: Oct 8, 2024

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