NM_000344.4(SMN1):c.388T>C (p.Tyr130His) AND Kugelberg-Welander disease

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 21, 2012
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000032709.3

Allele description [Variation Report for NM_000344.4(SMN1):c.388T>C (p.Tyr130His)]

NM_000344.4(SMN1):c.388T>C (p.Tyr130His)

Gene:

SMN1:survival of motor neuron 1, telomeric [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q13.2

Genomic location:

Preferred name:

NM_000344.4(SMN1):c.388T>C (p.Tyr130His)

HGVS:

NC_000005.10:g.70942472T>C
NG_008691.1:g.22532T>C
NM_000344.4:c.388T>CMANE SELECT
NM_001297715.1:c.388T>C
NM_022874.2:c.388T>C
NP_000335.1:p.Tyr130His
NP_001284644.1:p.Tyr130His
NP_075012.1:p.Tyr130His
LRG_676:g.22532T>C
NC_000005.9:g.70238299T>C

Protein change:

Y130H; TYR130HIS

Links:

OMIM: 600354.0020; dbSNP: rs397514518

NCBI 1000 Genomes Browser:

rs397514518

Molecular consequence:

NM_000344.4:c.388T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001297715.1:c.388T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_022874.2:c.388T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Kugelberg-Welander disease (SMA3)
Synonyms:: SPINAL MUSCULAR ATROPHY, TYPE III; SMA III; Muscular atrophy, juvenile; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009672; MedGen: C0152109; Orphanet: 70; Orphanet: 83419; OMIM: 253400

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000056472	OMIM	no assertion criteria provided	Pathogenic (Feb 21, 2012)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000056472

OMIM

no assertion criteria provided

Pathogenic
(Feb 21, 2012)

germline

literature only

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Genotype-phenotype relationship in 2 SMA III patients with novel mutations in the Tudor domain.

Fraidakis MJ, Drunat S, Maisonobe T, Gerard B, Pradat PF, Meininger V, Salachas F.

Neurology. 2012 Feb 21;78(8):551-6. doi: 10.1212/WNL.0b013e318247ca69. Epub 2012 Feb 8.

PubMed [citation]

PMID:: 22323744

Details of each submission

From OMIM, SCV000056472.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a 50-year-old French man with SMA type III (253400), Fraidakis et al. (2012) identified compound heterozygosity for a deletion of SMN1 (600354.0021) and a 388T-C transition in exon 3 of the SMN1 gene, resulting in a tyr130-to-his (Y130H) substitution at a highly conserved residue in the Tudor domain. The patient had 2 copies of SMN2 (601627). He had onset of slowly progressive proximal lower limb weakness in late adolescence, followed by upper limb involvement and cramps. He was wheelchair-bound at age 48. Physical examination showed severe motor deficit and amyotrophy in the pelvic and shoulder girdles, as well as severe motor deficit and amyotrophy in the distal limb muscles. EMG was consistent with severe chronic denervation at all extremities. Fraidakis et al. (2012) commented on the relatively mild disease course in this patient and suggested that there were likely compensatory factors affecting expression of the SMN genes.

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

Last Updated: Mar 26, 2023

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